Graphene Conduits For Lengthy Peripheral Nerve Defect Regeneration

ObjectivesPeripheral nerve defect injury occurs widely after severe trauma.It often results in sensory and motor dysfunction of the dominant area and greatly affects the quality of life of patients due to low curative rate.Nerve conduit implantation is becoming an alternative.In order to maximize the simulation of the growth environment in vivo,ideal nerve conduits should have the function of mechanical guidance,electrical conduction and stimulation of angiogenesis.However,most nerve conduits can only act as mechanical channels,and thus nerve repair is still not satisfactory.The study was aimed to prepare graphene oxide(GO)/polycaprolactone(PCL)conductive nerve conduits and to explore their roles in promoting the lengthy peripheral nerve defects regeneration as well as potential repair mechanisms.MethodsGO/PCL nerve conduit was prepared by an integrated molding technique.The conduit surface morphology and the GO nanoparticle structure were observed by scanning electron microscopy and transmission electron microscopy respectively.In addition,the interaction between GO and PCL,elastic modulus,elongation at break and scaffold conductivity were measured.Schwann cells were cultured on GO/PCL and PCL scaffolds in vitro.The cell morphological structure was observed on different scaffolds.Cytotoxicity,proliferation,adhesion and neural expression was evaluated by live & dead cell staining,CCK assay,immunofluorescence staining,Western Blot and quantitative PCR.After establishing 15-mm sciatic nerve defects in rat models,functional,electrophysiological,and histological outcomes were evaluated at 6,12,and 18 weeks after surgery.Meanwhile,we analyzed neurogenesis in the injured area,and furthermore,investigated the expression of angiogenesis related signaling pathways.ResultsGO/PCL conduit displayed multi-layered porous structures and showed excellent mechanical properties and electrical conductivity,and significantly promoted Schwann cell viability.In vivo experiments showed that axon and myelin sheath regeneration in the GO/PCL conduit group was similar to that of autograft transplantation and was significantly better than PCL counterpart.The GO nanoparticles release was positively correlated with the PCL degradation.In addition,GO/PCL conduit also induced angiogenesis.AKT-eNOS-VEGF signaling pathway may play an important role in this process.ConclusionsGO/PCL nerve conduit displayed good mechanical strength,electrical conductivity and biocompatibility.It significantly promoted lengthy peripheral nerve defects regeneration and stimulated angiogenesis.It should have great potential in the nerve tissue engineering.